The emergence of multidrug-resistant Helicobacter pylori in southeast asia:A systematic review on the trends and intervention strategies using antimicrobial peptides

The emergence of multidrug-resistant H. pylori poses a public healthcare threat, particularly in low- and middle-income countries. Recently, the World Health Organization has classified clarithromycin-resistant H. pylori as high priority in the research and discovery of novel antibiotics. This study was aimed to systematically review the prevalence of primary antibiotic resistance in H. pylori in Southeast Asian countries (SEAC) and to review current studies of antimicrobial peptides against H. pylori. We systematically searched through electronic databases of studies conducted on antimicrobial resistance of H. pylori in SEA countries. Furthermore, we searched articles that conducted studies on antimicrobial peptides, naturally occurring host’s defense molecules, against H. pylori. After a series of screening processes, 15 studies were included in our systematic review. Our analysis revealed that primary resistance of H. pylori to metronidazole, clarithromycin, and levofloxacin were high in SEAC, although the primary resistance to amoxicillin and tetracycline remains low. Multidrug-resistant H. pylori are emerging in SE Asian countries. The antimicrobial peptides show promising antibacterial and antibiofilm activity against drug-resistant H. pylori. The research and discovery of antimicrobial peptides against H. pylori in SEAC will help in limiting the spread of antimicrobial resistance of H. pylori

In vitro study of anti-Helicobacter pylori activity of honey: a systematic review

This review explores the beneficial effects of honey on Helicobacter pylori-induced gastric ulcer and duodenal ulcer. The research of the effectiveness of honey on H. pylori infection using electronic databases was done, these include Medline via Ovid Medline, Scopus and ScienceDirect published from the year 2000 to 2018. The articles were evaluated and selected based on the criteria which report on the effects of honey on gastric ulcer and duodenum ulcer caused by H. pylori infection. There are 53 articles were identified, which stated to the studies that relate to the criteria. Afterwards, nine articles on honey and its extracts were selected and assessed accordingly in this review. All studies reported positive effects of honey on H. pylori-induced gastric ulcer and duodenal ulcer. Most of the studies showed at minimum 10% of honey concentration were effective as anti-H. pylori activity. This systematic review emphasized the potential of honey used to inhibit the H. pylori infection in-vitro. Future extensive studies are required to find the active component and molecular mechanism of honey before animal and human observational studies could be conducted to deliver valid evidence

Infeksi Mycobacterium tuberculosis: data demografi dan perbandingan ujian kerentanan anti-tuberkulosis

Tuberkulosis merupakan masalah utama dalam kesihatan awam di kebanyakan negara membangun termasuklah Malaysia. Di Malaysia, bilangan kes kematian disebabkan tuberkulosis menurun tetapi yang membimbangkan adalah apabila terdapat peningkatan kes kerintangan Mycobacterium tuberculosis terhadap ubat-ubatan sedia ada. Dalam kajian ini, data demografik pesakit telah dianalisis dan kerintangan M. tuberculosis terhadap agen anti-tuberkulosis (Isoniazid, Streptomycin, Rifampicin dan Ethambutol) telah dikenal pasti dengan menggunakan ujian kerentanan plat MYCOTB. Sejumlah 40 pencilan klinikal M. tuberculosis yang dipencil daripada pesakit di PPUKM telah dipilih secara rawak. Dalam kalangan pesakit tuberkulosis, seramai 62.5% adalah lelaki (purata umur: 36.9+17.9 tahun) manakala 37.5% adalah wanita (purata umur: 42.6+16.6 tahun). Pesakit berbangsa Melayu mencatatkan peratusan tertinggi iaitu 60%, diikuti pesakit India 15%, Cina 5% dan lain-lain bangsa 20%. Pemencilan M. tuberculosis daripada sampel klinikal adalah masing-masing 60%, 17.5%, 7.5%, 7.5%, 5% dan 2.5% daripada kahak, aspirat trakea, nanah, darah, larvaj bronkoalveolar dan tisu. Ini berhubung kait dengan pesakit Tuberculosis yang majoritinya (67.5%) hadir dengan simptom batuk berpanjangan. Keputusan ujian kerentanan antara MYCOTB dan BACTEC MGIT 960 telah dibandingkan. Purata masa yang diperlukan untuk ujian kerentanan anti-TB menggunakan plat MYCOTB dan BACTEC MGIT 960 ialah masing-masing 2 dan 40.5 minit. Kos setiap sampel bagi plat MYCOTB dan BACTEC MGIT 960 adalah masing-masing RM16.65 dan RM42.87. Sebagai kesimpulan, berdasarkan data demografik, jangkitan TB dalam kalangan pesakit lelaki kaum Melayu adalah yang tertinggi sementara kahak merupakan spesimen yang paling banyak diterima. Penggunaan plat MYCOTB adalah lebih baik berbanding BACTEC MGIT 960 dan keputusan ujian kerentanan menunjukkan pencilan klinikal tersebut adalah 100% rentan kepada agen anti-TB yang diuji. Data yang diperoleh boleh digunakan sebagai maklumat dalam pengemaskinian panduan diagnosis dan rawatan TB pada masa hadapan

Rapid detection and E-test antimicrobial susceptibility testing of Vibrio parahaemolyticus isolated from seafood and environmental sources in Malaysia.

Objectives: To find out the prevalence and antimicrobial susceptibility of Vibrio parahaemolyticus in seafoods and environmental sources. Methods: The study was carried out at the Center of Excellence for Food Safety Research, University Putra Malaysia; Universiti Kebangsaan Malaysia; Medical Molecular Biology Institute; and University Kebansaan Malaysia Hospital, Malaysia between January 2006 and August 2008. One hundred and forty-four isolates from 400 samples of seafood (122 isolates) and seawater sources (22 isolates) were investigated for the presence of thermostable direct hemolysin (tdh+) and TDH-related hemolysin (trh+) genes using the standard methods. The E-test method was used to test the antimicrobial susceptibility. Results: The study indicates low occurrence of tdh+ (0.69%) and trh+ isolates (8.3%). None of the isolates tested posses both virulence genes. High sensitivity was observed against tetracycline (98%). The mean minimum inhibitory concentration (MIC) of the isolates toward ampicillin increased from 4 ug/ml in 2004 to 24 ug/ml in 2007. Conclusions: The current study demonstrates a low occurrence of pathogenic Vibrio parahaemolyticus in the marine environment and seafood. Nonetheless, the potential risk of vibrio infection due to consumption of Vibrio parahaemolyticus contaminated seafood in Malaysia should not be neglected

Molecular characterization and prevalence of antibiotic resistance in Helicobacter pylori isolates in Kuala Lumpur, Malaysia

Acknowledgment We would like to thank the Universiti Kebangsaan Malaysia for providing both the permission and the facilities to conduct and publish this research. The research was funded by a grant from Universiti Kebangsaan Malaysia under Economic Transformation Programme Research Fund Scheme (grant no. ETP-2013-042).Peer reviewedPublisher PD

The heterogeneic distribution of Helicobacter pylori cag pathogenicity island reflects different pathologies in multiracial Malaysian population

BACKGROUND: Helicobacter pylori harbouring cag-pathogenicity island (cagPAI) which encodes type IV secretion system (T4SS) and cagA virulence gene are involved in inflammation of the gastric mucosa. We examined all the 27 cagPAI genes in 88 H. pylori isolates from patients of different ethnicities and examined the association of the intactness of cagPAI region with histopathological scores of the gastric mucosa. RESULTS: 96.6% (n = 85) of H. pylori isolates were cagPAI-positive with 22.4% (19/85) having an intact cagPAI, whereas 77.6% (66/85) had a partial/rearranged cagPAI. The frequency of cag2 and cag14 were found to be significantly higher in H. pylori isolated from Malays, whereas cag4 was predominantly found in Chinese isolates. The cag24 was significantly found in higher proportions in Malay and Indian isolates than in Chinese isolates. The intactness of cagPAI region showed an association with histopathological scores of the gastric mucosa. Significant association was observed between H. pylori harbouring partial cagPAI with higher density of bacteria and neutrophil activity, whereas strains lacking cagPAI were associated with higher inflammatory score. CONCLUSIONS: The genotypes of H. pylori strains with various cagPAI rearrangement associated with patients’ ethnicities and histopathological scores might contribute to the pathogenesis of H. pylori infection in a multi-ethnic population

The Role of Antimicrobial Peptides as Antimicrobial and Antibiofilm Agents in Tackling the Silent Pandemic of Antimicrobial Resistance

Just over a million people died globally in 2019 due to antibiotic resistance caused by ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The World Health Organization (WHO) also lists antibiotic-resistant Campylobacter and Helicobacter as bacteria that pose the greatest threat to human health. As it is becoming increasingly difficult to discover new antibiotics, new alternatives are needed to solve the crisis of antimicrobial resistance (AMR). Bacteria commonly found in complex communities enclosed within self-produced matrices called biofilms are difficult to eradicate and develop increased stress and antimicrobial tolerance. This review summarises the role of antimicrobial peptides (AMPs) in combating the silent pandemic of AMR and their application in clinical medicine, focusing on both the advantages and disadvantages of AMPs as antibiofilm agents. It is known that many AMPs display broad-spectrum antimicrobial activities, but in a variety of organisms AMPs are not stable (short half-life) or have some toxic side effects. Hence, it is also important to develop new AMP analogues for their potential use as drug candidates. The use of one health approach along with developing novel therapies using phages and breakthroughs in novel antimicrobial peptide synthesis can help us in tackling the problem of AMR

Ethnic differences in the prevalence, clinical outcome and cag Pathogenicity Island (cagPAI) virulence gene profiles of Helicobacter pylori strains from Malaysia

Different Helicobacter pylori genes may be well conserved within different ethnic groups and could give rise to different clinical outcomes. In this study, we demonstrated a low prevalence of H. pylori infection (19.2%) which is in concordance with the current trend demostrated locally and abroad. The Indians had the highest prevalence of H. pylori infection among other ethnic groups (Malays= 8.6 %, Chinese= 24.3 %, Indians= 33.9%). cagM and cagT were the most predominant genes found (63.4% for each), followed by cagA (62.2 %), cagE (48.2%), cag6-7 (46.3%), cag10 (42.1%), cag13 (4.9%) and IS605 (3.7%). No significant association was found between H. pylori infection and H. pylori genes with ethnic groups or clinical outcomes. Indians who had a combination of cagA/ E/M genes of H. pylori were likely to be associated with 21-time of having non-ulcer dyspepsia (NUD) than peptic ulcer disease (PUD). Therefore, these genes may serve as useful markers in predicting the clinical presentation of a H. pylori infection among Indians in our studied population. Hence, this preliminary data might explain why Indians have a low prevalence of gastric cancer and peptic ulcer disease despite having persistently high prevalence of H. pylori infection for many decades (“Indian enigma�) in Malaysian patients

Immunophenotyping of gastritis, gastric ulcer and gastric cancer using a cluster of differentiation (CD) antibody microarray

One of the factors that contribute to the development of gastric cancer is the host immune response. Extensive immunophenotype of gastric cancer can be identified by using antibody microarray technique that profiles more than 100 cluster of differentiation (CD) antigens in parallel. In this study, we used DotScanTM antibody microarray to profile CD antigen expression in patients with distinct digestive diseases for surface antigen disease-signatures. Patients’ blood samples with gastric disorders and healthy controls were taken and processed for leukocytes isolation using Histopaque density gradient centrifugation. Leukocytes were captured onto DotScanTM slides and cell binding densities were analyzed using DotReaderTM. Different groups of gastric diseases were found to be characterized by differentially expressed distinct CD antigens. Compared to normal healthy controls, 17, two and four highly expressed CD antigens were identified in gastritis, gastric ulcer and gastric cancer patients, respectively. The 17 CD antigens that show differential expression in gastritis were CD15, CD16, CD20, CD23, CD24, CD25, CD28, CD34, CD37, CD77, CD102, CD103, CD122, CD128, CD10, CD183, and CD184. High expression of CD64 and CD69 were found in gastric ulcer, whereas CD52, CD126, CD135, and CD121a were highly expressed in gastric cancer. CD antigens involve in T-cell functions had reduced expression in gastric cancer, while proinflammatory cytokines shows increased expression. These results demonstrate specific immunophenotype of CD antigens in patients with various gastric diseases and identification of differential expressed surface antigens may have clinical significance for diagnostic and therapeutic purposes

Helicobacter pylori cagA gene variants in Malaysians of different ethnicity

We have defined DNA repeat variability in the 3′-terminus of the cagA gene of Helicobacter pylori strains from Malaysian patients of different ethnicities. We identified different alleles based on the EPIYA repeats. cagA types A-B-D and A-B-B-D are more similar to the sequence of Japanese strains, whereas cagA types A-B-C, A-B-C-C, A-B and A-C displayed similarity to strain 26695 sequences. A significant association was found between cagA genotypes and patients’ ethnicity, with cagA type A-B-D being predominantly isolated from Chinese patients and cagA type A-B-C from Malays and Indians. Our data further corroborate the possibility that variant biological activity of CagA may affect the host specificity and/or pathogenicity of H. pylori